urqLeuropsiquiatrLfddiojgUeVneldaeli xepartm entL ofL eurolo gy ostock

urqLeuropsiquiatrLfddiojgUeVneldaeli xepartm entL ofL eurolo gy ostock - Description

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urqLeuropsiquiatrLfddiojgUeVneldaeli xepartm entL ofL eurolo gy ostock

brPage 1br urqLeuropsiquiatrLfddiojgUeVneldaeli xepartm entL ofL eurolo gy ostockL nive rsityL Uo stock L erma nyVoL xepartm entL ofL eurol ogy 305lin ik o rdbeidb rgL Uam urg ermanyVoL xep

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urqLâeuropsiquiatrLfddiojgUeVneldaeli xepartm entL ofL âeurolo gy êostockL ônive rsityL Uêo stock ‘L `erma nyVoL xepartm entL ofL âeurol ogy ılin ik âo rdb´eidb rgL U´am urg `ermanyVoL xepartmentLofLâeurology ‘LíoLãauloLôniversityLáedicalLíchoolLUíoLãaulo‘LvrazilVb êeceivedLgLxecemberLfddg‘LreceivedLinLfinalLformLfLíeptemberLfddhbLucceptedLeiLâovemberLfddhb Dr nWDirkWDresslerWmWGehlsheimerWStr nWrplWDmqxqtwWRostockWhGermanyinWEmmail®Wdirkndressler@mednunimrostocknde BOTULINUM´TOXIN áechanismsLofLaction DirkWDressler lWFereshteWAdibWSaberi

lWEgbertoWReisWBarbosa uvíóêuwóL aL óhisL reviewL describesL therapeuticallyL relevantL mechanismsL ofL actionL ofL botulinumL toxinL UvóVb vLóL sL mo le cu lar mo de fL ctio inc lud sL xtr ac ellu lar bin in gL oL lyc pr ot ein eL tru ctu re sL ch line rg icL rve terminalsL andL intracellularL blockadeL ofL theL acetylcholineL secretionbL vóL affectsL theL spinalL stretchL reflexL by blockadeL ofL intrafusalL muscleL fibresL withL consecutiveL reductionL ofL ˆacˆˆL af ferentL signalsL andL muscleL tone withoutL affectingL muscleL strengthL UreflexL inhibitionVbL óhisL mechanismL allowsL forL

antidystonicL ef fectsL not onlyL causedL byL targetL muscleL paresisbL vóL alsoL blocksL ef ferentL autonomicL fibresL toL smoothL musclesL andL to exocrineLglandsbLxirectLcentralLnervousLsystemLef fectsLareLnotLobserved‘LsinceLvóLdoesLnotLcrossLtheLblooda brainabarrierLandLsinceLitLisLinactivatedLduringLitsLretrogradeLaxonalLtransportbLˆndirectLcentralLnervousLsys te mL ef ec tsL in clu eL efle inh ib itio ‘L no rm alis atio fL re cip ro ca lL in ibit ion ‘L in tra co rt ica lL inh ib itio an so ma

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lev an tesLparaLaLcompreensoLdoLseuLusoLteraputicobLuLaoLdaLóvLaLnvelLmolecularLconsisteLnaLsuaLligaoLex tr ce lu la es tr tu sL li co t ic sL te mi ai sL rv sL lin ico lo io in ra lu la rL cr deLacetilcolinabLuLóvLinterfereLnoLreflexoLespinalLdeLestiramentoLatravsLdoLbloqueioLdeLfibrasLmusculares ntrafusai sL causando ed uoL daL si al izaoL aferenteL vei culadaL po fibras ˆaL eL ˆL eL doL tono cular ãortanto‘L oL efeitoL daL óvL podeL estarL relacionadoL noL somenteL L paresiaL

muscularL masL tambmL L inibio re fl bL in io ib ic sL ra sc lo is la cr upe sarL oco rre rL alg maL ifu so sist mica ap sL ap lica o int ram usc ula rL aL vL o ting eL siste maL rvo soLcentralLUíâwVLdevidoLaoLseuLpesoLmolecularLUnoLatravessaLaLbarreiraLhematoenceflicaVLeLLlentidoLdo seu tra spo rte ax na lL ret rg ra do eL erm iteL su aL in ativ a o bL àsL ef eito sL in dire to sL so reL íâw s onL in ibi o

reflexa‘LreversoLdasLalteraesLdaLinibioLrecproca‘LdaLinibioLintracorticalLeLdeLpotenciaisLevocadosLso matosensoriaisbL uL reduoL daL dorL induzidaL porL formalinaL sugereL queL aL óvL tenhaL efeitoL analgsicoL direto possivelmenteL mediadoL porL bloqueioL daL substnciaL ‘L doL glutamatoL eL doL peptdeoL relacionadoL aoL gene daLcalcitoninabL uLçLu õLêLuLíLaLwL´Lu to l ic ‘L is sL ‘L ti lc li ‘L sL la so re le st ir to Lm lo lis ‘L l la Le in ‘L ra La Lr r ra Lb rr ir Lh ma lic ‘L

stnciaLã votul numL tox nL vóV ha sL beenL perce vedL as ea gLuLiLlLd co du tLiLoLn sL rL ou ce of ot ul mb th em tLh en ur tLhLe `e ma nL di tr ct hy si ci an ˜us ti nus rn er ubl she tw oL monogra phsL descr ibi ngL the cl ni cal fe ature sL of botul sm it hL aL preci si onL ti unsurpa ssed today eL‘Lf nL heL mkd sL theL perce pti onL of vó be ganL oL cha nge henL it as us edL asL aL res earchL tool toL study spi nal cor dL phy si ol gy nL th eL ea rl em ld sL vó erc ept on chan ged co mpl ete henL sL th er ape uti ote nti suddenl beca meL ppare ntb àv erL heL pa stL dL ear hasL

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chainL polypeptideL withL aL molecu larL massL ofL approximatelyL eidkxbL ˆtL isL activated ly ly ic cleavedLintoLtheLeddkxLheavyLchainLandLtheLidkx lightL chainbL votulinumL neurotoxinL existsL inL seven differentL serotypesL namedL u‘L v‘L w‘L x‘L y‘L zL andL `b lt llL in ib yl cholineL releaseL fromL nerveL terminals‘L theirL intra cellularLtargetLproteins‘LtheirLcharacteristicsLofLac tionL andL thei rL poten ci esL aryL substantial vóL ty pe uL Uv VL ha sL ee nL heL mos tL de yL st udi dL er oty forLtherapeuticLpurposesbLáoreLrecentlyLvóLtypeLv Uvó avVLbecameLcommerciallyLavailableb

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exocrineL gland‘L theL glandular se cre ti on sL bl ock edb óh eL hi bi onL of cet chol ex ocy tos sL by vó sL te rmi na te dL by est orat onL of th íâuêyL proteinL complexL turnover bL uxonalL sprout ngL andL endpl ate el onga ti onL occu rs bu tL sL be ev toL beL aL tra si entL hen omen onL no tL resp ons eL for theLterminationLofLtheLvóLeffect BotulinumWtoxinWactionWonWtheWstriateWmuscle DurationWofWactionW úhenLvóLisLinjectedLintoLa striateL musc e paresi sL occ ursL fterL tw to fiv eL days an dL st ro oL to hr on th sL be or ra ua al yL st art sL toL ear of zi gure eL gi ve sL anL ex am

pl eL of vLóL sL durati nL acti nL asL reconstructedL fromL aL paa tLiLeLnLtL sL re nt nd he nL nt od st vóLareLformed‘LasLinLthisLexample‘LtheLdurationLof actionLandLtheLextentLofLtheLmaximalLtherapeutic eLf ec tL re us ua edu ced ft er fe vó ppl cat ons ablenW ConditionsW forW whichW treatmentW withW botulinumW toxin hasWbeenWtriedWhDressler lWrpppin áovementLxisorders xystonia ´emifacialLípasm remor ics vruxism êeainnervationLíynkinesiasL áyokymia âeuromyotonia ítif fLãersonLíyndrom ípasticity ´ypersecretoryLxisorders ´yperhidrosis íialorrhea ´yperlacrimation êhinorrhea àphtalmicLxisorders

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elf urqLâeuropsiquiatrLfddiojgUeV UpartialLtherapyLfailureVLbeforeLcompleteLtherapy failureL occurs bL óheL subjectiveL durationL ofL ti on

vari esL et weenL tientsL suffe ringL ro heL sLaLmLe cond ti nL and et ee nL pa ti nt sL su fe ri gL fromLdLiLf fere ntL condi ions henL theL ame pat entL is treat edLwithLidenticalLtreatmentLparametersLtheLdura tionLofLactionLisLusuallyLstableb DWoWsWeWmWeWf ectW correl ti onW us show nL nL fi gureL f th er sL co rr ti nL be en th eL oun fL óL pa pl ie dL ndL the xt entL ofL pares sL pr ovok ed ´ow ea vLeLr re ati el yL ow vóL dose sL ready produceL subsa ta ti al re os ef fe tL co re nL cu rv ca nL be ti nL cor re ti ons how er ha eL oL be ep tL db DosemdurationWcorrelationW

aLóhereLisLalsoLaLcor relationL betweenL theL amountL ofL vóL appliedL and theL durati nL ofL tsL action ever th sL co rrel aa tionL se emsLtoLexistLonlyLwhenLrelativeLlowLvóLdos esLareLusedbLúithLhigherLvóLdosesLtheLdurationLof actionLseemsLtoLsaturateLatLaboutLthreeLmonthsb MuscleWatrophyWmW úhenLvóLisLinjectedLintoLaLhy per act eL usc eL heL nduce dL are si pr oduce sL aL ea duc on fL he di am te of he ar ge mu sc úLhLeLn heL targ etL musc isL hype rtro phic ueL to lon gL as ta ingL hyperacti vi tyL vó ai nd ucedL paresi sL canL normal ise itsL si zeb úhenL vóL sL giv enL ov erL aL prol

ngedL ri od mLuLs igW tm tW pr of ile ofW pa ti nt ith ce rv ic lW st onia ndW nt ibo dy min duc dW bo tul inum ox inW he py fa lur nW he pr of ile ons tr uc dW fr om tr ntW le da rW nW hic hW th pa ti nt sWa dWtoWdoc um tWth ra ll Wse it yWof Wa llWc rv ca st onia Wr la dWco pla in ts nWa to Wba si sn eWre le sWt he Wunt re dWc ond iti onlWp Wla WofWa ny Wc om pl int sn WInje ionWs ie dW pr oduc de qua he pe ut ic fe sl he sW inj ct io nW ie sW doe no tW pro duc th ra pe tic ts Wh om ple the ra py ilur in WA ll Wot he inje ionW ri sW pr oduc re duc dW the pe ut ic We ts Wh pa rt ia Wt he ra

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urqLâeuropsiquiatrLfddiojgUeV elg cl tr oph yL sL not nL bl at eL vó ef fe ct an dL an th ea reforeLnotLbeLusedLtoLtestLvóLefficacy DilutionWef fectWmW ˆtLhasLbeenLassumedLthatLwith higherL vóL dilutionsL theL

tissueL dif fusionL ofL vóL can beLincreased‘LthusLinfluencingLtheLtherapeuticLef fectLandLtheLsideLeffectsLofLaLvóLtherapy bLíoLfar ‘Lno va dL stu die sL reL av ai abl eL toL sti ate opti al di ua tionLforLdifferentLtherapeuticLsituationsbLxefining mLoLuLsLe unitsL toL compareL theirL therapeuticL potenciesL has puzzledLneurologistsLforLyearsbLˆnitialLstudiesLused nadequat eL cl ni cal mode ls suchL sL bl ephar ospasm hemifacialL spasmL orL spasmodicL dysphonia‘L which are ex tre mel dose nsens it veL it hL re spectL toL the hera peu ticL ou tco meL and sid eL effec tsbL ec ent êanoux etL al

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ferencesWfromWtheWmuscleWspindleWorgansWandWtheWGolgiWtendon or ga cont rolW the lpha one uro nW it nne in gW th lW us le nW Whe nW he le lW usc le is tre che dW us cle pindle sWconv igna lW toWthe alphaW motoneuronW whichW then stimulatesWtheWcontractionWofWbothWintrafusalWandWextrafusalWmuscleWfibresnW
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elh urqLâeuropsiquiatrLfddiojgUeV aLf fec ti ng he us cl eL pi ndl func ti on eLh thL th di ul ou dL eLi óL ro uc sL diffe re tL effe ts th mu cle spindleL rgansb êo sa lesL tL al eLj demon stratedL atro ph inL both extrafu sal andL intrafusalL muscleL fibres

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targetL muscleL paresisL butL alsoL byL spinalL reflex inhibitionb BotulinumWtoxinWactionWonWtheWautonomicW nervousWsystem óL an eL us ed tr ea tL hy pe ra ct iveL sLmLoLoLtLh usc es su chL sL he di ta oe sop ha gea sph ct erL cha th phi nc te ddi nL sp hi ct dd fun cti on he te rna na phi nc te rL anal fi ssure nd ni s th us nL dLeLtLrLuLsLoLr aLsLpLhLiLnLc terL dyssynergiaL andL theL pylorusL inL gastroparesisb íystemicLadverseLeffectsLofLvó avLalsoLdemonstrate smoothL muscleL affectionL ofL vóL whenL heartL burn occurs el bL úhenL vóL isL usedL toL treatL hyperhidrosis hypersalivation‘L

hyperlacrimation‘L orL whenL vó av adverseLef fects‘LsuchLasLdrynessLofLeyeLorLmucosal drynessL occurs el ‘L exocrineL glandularL tissueL isL af fectedLbyLvó bLvó ‘LthereforeLcanLaffectLtheLef ferent fibre sL fL theL au ton omicL ner usL systemL asL alread us ri dL by us nu rn nL he ar lyLem th century e‘f bLíoLfar ‘LitLseemsLthatLvóLactionLon ic er ys mL fLeLr fr omL tsL acti on onL heL str at eL ne urom uscu arL sy napa seb ucti nL onL theL au tonomi rvousL system of fLeLrLs an dd ona ch an ceL oL st udy do se ef fe ct nd dLoLsLeLa durat onL el ati ons hip sb het herL vóL al soL af fe ctsL

tLhLe aLf er nt ra sm on of eL au to no mi cL er us sa temLitLneedsLtoLbeLstudiedb BotulinumWtoxinWactionWonWtheWcentralW nervousWsystemWhCNSi DirectW effectsW mW úhenL vóL isL injectedL intoL aL tar etL tissu eL itL almo stL co mp telyL ou nd oL he axon terminal eLm bL ´o ever whenL vó auL sL appli ed to tr er ca to ni sm ct on of th pp vóLareLdistributedLsystemicallyLandLcanLbeLdetect ed cr as fL ne ur om us cu rL er nL no na iLnLjLeLcLt edL muscles fd bL úhenL vó avL isL appliedL toL treatL cervi alL ton su bs tant ystemic an ti ho li erg sideLef fectsLcanLbeLclinicallyLdetected el

bLxespiteLits systemicLdistributionLdirectLvóLef fectsLonLtheLwâí haveL no beenL re ort ed‘L sinceL bo numL neurotoa nL th sL of id ca nno tL pen et at eL the oa odLbrainLbarrier bLupartLfromLsystemicLpenetration vóLcouldLalsoLreachLtheLwâíLbyLretrogradeLaxonal tr ns po rt nd ee uc hL ro gr ad ona tr ns po ha nL de te hL ct otu inu mL euro toxin fLe bL ´o ever th eL etrog rad axonalL transportL wasL soL slowL thatL theL appliedL vó wasLlikelyLtoLbeLinactivatedLbeforeLitLreachedLthe íb ranssynapticL transportL wa sL otL observedb vó actionL uponL êenshawL cellsL wasL onlyL demonstrat

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supraspinalL levelL vó canL normal seL al teredL intr acorti cal nh bi ti on fLi aLnLd al te re dL so ma os en sor ok dL ot en ti fLj ul tho ua hL vóL can enhan ceL so meL as pect sL fL cort al activaa tionLitLfailsLtoLimproveLtheLimpairedLactivationLof theLprimaryLmotorLcortexLseenLinLwriter sLcramp fk BotulinumWtoxinWactionWonWpain úhenLvóLisLusedLtoLtreatLpainfulLmuscleLhyper ac iv ity di so rdersL frequen tl sub tan ial pai nL rel ie isL reportedbL íoL far ‘L thisL painL reliefL wasL attributed toL the ed uct onL ofL the us cl hy pe ra ct ty ´o ea ver ‘L formalinainducedL painL inL

animalsL canL beL re yL óL ire na lg sic ef fLeLcLt fLl bL ro ly suchL ef fectL ofL vóL isL basedL onL anL actionL onL neuro transmittersLotherLthanLacetylcholineb íubstanceL ãL UíãV‘L aL neuropeptideL involvedL in painL perception‘L vasodilationL andL neurogenicL in flammation‘L canL beL blockedL byL vóL togetherL with
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